The goal of the ongoing research in our laboratory is to find effective and long-lasting treatments to reduce the cognitive, sensory and motor impairments associated with acute, traumatic injury to the brain. The specific purpose of the research described in this proposal is to determine the extent to which the hormone, progesterone, can improve the rate and extent of behavior and anatomical recovery of function following traumatic brain injury. We will use a contusion model of frontal cortex injury to mimic the head trauma common in patients who have suffered severe concussions or blows to the cranium such as those that might occur in a head-on automobile collision. Following the contusion injury, we will seek to determine, among other questions, whether; (1) there is a "window of opportunity" during which progesterone must be given in order to be effective in reducing cognitive and sensory deficits in head-injured animals; (2) progesterone can restore blood-brain-barrier integrity after brain injury so that more normal CNS metabolism can be induced after trauma; (3) progesterone exerts its beneficial effects by blocking injury-induced inflammation, production of free-radicals and subsequent lipid peroxidation of vulnerable nerve membranes; and (4) are the beneficial effects of progesterone age-dependent -- will similar effects be seen in aged male and female rats with head injury? This research will not only provide a better understanding of the anatomical and behavioral consequences of head trauma, but m ay also lead to a cost effective, easily implemented course of treatment which could result in an improvement of quality of life for thousands of head injury victims.